KR-31378 ameliorates atherosclerosis by blocking monocyte recruitment in hypercholestrolemic mice

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Title
KR-31378 ameliorates atherosclerosis by blocking monocyte recruitment in hypercholestrolemic mice
Author(s)
Ji Yun Kim; Ki Hoan nam; S O Kim; Jae Hoon Choi; Hyoung-Chin Kim; S D Yang; Joo Hyoung Kang; Young Han Ryu; Goo Taeg Oh; S E Yoo
Bibliographic Citation
FASEB Journal, vol. 18, no. 6, pp. 714-716
Publication Year
2004
Abstract
The recruitment of monocytes into the artery wall is a crucial early step in atherogenesis. A novel compound, KR-31378, has been shown to be a neuroprotective agent for ischemia-reperfusion damage in rat brain via its potent antioxidant and antiapoptotic actions. Here, we report the effects of this compound on atherogenesis and possible mechanisms of action. In Ldlr knockout mice fed with a high-fat, high-cholesterol diet, treatment with KR-31378 significantly inhibited fatty streak formation and macrophage accumulation. To address the possibility that KR-31378 may influence the initial stages of atherogenesis, we examined its effect on the adhesion and migration of monocytes to endothelial cells stimulated with tumor necrosis factor-alpha. KR-31378 decreased the adhesion in a dose-dependent manner. The observed decreases in cell adhesion and migration correlated with KR-31378-mediated down-regulation of vascular cell adhesion molecule-1 (VCAM-1) and interleukin (IL)-8. Nuclear factor-kappaB (NF-kappaB) is known to regulate the expression of adhesive and chemotactic molecules including VCAM-1 and IL-8. Indeed, transient transfection experiments, electrophoretic mobility shift assay, and IkappaB degradation assay showed that KR-31378 decreased NF-kappaB activation. These results indicate that KR-31378 potently reduces fatty streak formation by inhibiting NF-kappaB-dependent cellular adhesion and chemotactic molecule expression, which are crucial to monocyte infiltration into the arterial wall during the early stages of atherogenesis.
ISSN
0892-6638
Publisher
Wiley
DOI
http://dx.doi.org/10.1096/fj.03-0652fje
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > 1. Journal Articles
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